The new capsule blasted off aboard the Falcon 9 rocket built by SpaceX - run by billionaire Elon Musk - at 2:49 am (0749 GMT) from the Kennedy Space Center at Cape Canaveral, Florida, lighting up the coastline. Instead of an actual human, the Crew Dragon carried a lifelike anthropomorphic test "device" lovingly called Ripley that had sensors to help determine the potential effects of the trip on actual humans.
A veteran of two spaceflights, Garrett Reisman left NASA in 2011 to play a senior role in the development of the Crew Dragon spacecraft at SpaceX until past year.
Behnken said he was "super excited" by the Dragon successfully docking at the ISS. The SpaceX company employees cheered until the capsule reached orbit.
The spacecraft is created to carry up to seven passengers to the space station, but for this flight, the capsule is loaded up with 450 pounds of cargo and a test dummy outfitted in one of SpaceX's customised spacesuits.
Starliner and Dragon 2 – via Nathan Koga for NSF L2
NASA selected SpaceX and Boeing to design and build crew-carrying spacecraft to shepherd astronauts to and from the space station - replacements for the Space Shuttle, which NASA retired in 2011.
"We are not in a space race", he said.
"Today's successful launch marks a new chapter in American excellence, getting us closer to once again flying American astronauts on American rockets from American soil", NASA administrator Jim Bridenstine wrote in a statement.
Applause broke out at SpaceX's control centre in Hawthorne, California, as Crew Dragon, and its "astronaut dummy" Ripley, secured itself to the station with a set of hooks and latches.
The unmanned capsule will be docked automatically in a World first, as the worldwide docking adapter aboard the ship will be utilised for the first time. "We've got to dock to the space station and come back".
"We're going to have more access to space at a better cost than at any point in human history", said Bridenstine, adding he was "100 per cent confident" that a manned flight would happen by the year's end.
The crew capsule is based on the ISS cargo freighter but incorporates life-support systems and more powerful thrusters to push the vessel to safety if something goes wrong with the rocket.
Saint-Jacques and Kononenko were the first to enter the Crew Dragon after opening the hatch.
This beefed-up, redesigned Dragon is the first American-made, designed-for-crew spacecraft to pull up to the station in eight years.
Dragon crew capsules will splashdown in the Atlantic not far from Kennedy.